Signatures and circuits of novelty-like cells in hippocampal CA1 in a mouse model of Alzheimer‘s disease
1 IEECR
The loss of memories is the earliest and often most detrimental symptom in the course of Alzheimer’s disease (AD), the most common form of dementia. The loss of neuronal cells, which some of are assumed to carry mnemonic information, suggests itself to be the leading cause of memory loss. Besides, the question of alternative mechanisms has been raised. Our lab recently showed that an additional cell ensemble in hippocampal CA1, so-called novelty-like cells, interfered with the engram and thus, impaired memory recall. This suggests a novel mechanism of memory impairment. However, the exact circuit that leads to the evocation of the interfering ensemble is still not known. A potential candidate circuit involves the actions of a specific type of somatostatin (SST)-expressing inhibitory interneurons, O-LM interneurons. In this project, we will address the role of O-LM interneurons during hippocampus-dependent associative learning. We expect the chemogenetic inactivation of O-LM interneurons during memory formation to mimic the interfering ensemble during memory recall and thus, cause recall impairment. By using further chemogenetic tools and behavioral tasks we try to answer the question whether this interfering ensemble is associated with novelty. Conversely, in a mouse model of AD, chemogenetic activation of O-LM interneurons may be sufficient to prevent novelty-like activity in CA1. The analysis of neuronal activity will be performed by examining the immediate early gene cfos at the transcriptional and protein level, using RNA-FISH and immunohistochemistry, respectively.